Silicon (Si) has only recently been recognized as a trace element essential for developmental processes and bone formation in mammals, whereas silicate dusts and asbestos fibers have aroused widespread concern for many years as being causative agents in fibrotic lung diseases and, recently, cancer. Nevertheless, the biological role of silicon is just beginning to be investigated, due in part to the great difficulties inherent in silicon biochemistry. In the diatom, however, with its absolute requirement for Si, these difficulties are largely overcome, and we have been able to show that in this organism Si enters the cell by a carrier-mediated, Na ion -driven active transport system, and is required for a great variety of basic processes including DNA replication, i.e., synthesis of DNA polymerases, as well as polypeptides and cAMP and cGMP. Our primary objective is to study Si metabolism in terms of the role of Si in health and pathology, using the diatom as a model experimental system. We propose to continue our studies on Si-transport by investigating the mechanism of energy coupling, including the Si-Na ion relationship; we will identify the molecular form of the transported silicate by characterizing any Si-carrier(s) and the silicate pump. We will identify the silicate ionophore we found, and attempt to elucidate its biological role. We wish to see the extent to which silicate affects gene expression and to determine the level at which the Si-dependent DNA polymerases synthesis occurs. We propose further to determine how Si controls cAMP and cGMP levels; the effects of cAMP and cGMP on synthesis of DNA polymerases and DNA polymerase mRNAs and to see whether Si controls DNA synthesis through polyamines. In addition, we will investigate in the electron microscope the spherical Si particles constituting the wall of a diatom.